This application for support of years 11 through 15 of the Mental Retardation Research Center (MRRC) at the Kennedy Krieger Institute and John Hopkins University is submitted in response to RFA HD-97-003. The MRRC consists of an administrative core (Core A) and five research cores (Cores B, C, D, E, and F). The Core A (Administrative), provides overall management and organizational support to the Center, operates overall management and organizational support to the Center, operates the educational component (lectures and seminars) and links users to biostatistical services. Core B (Genetics) provides centralized tissue culture, amino acid, organic acid analyses, standard and molecular cytogenetics, specialized molecular genetics (DNA and RNA analyses) and bioinformatics. Core C (Neuroscience) provides synaptic neurochemistry (focusing on histology imaging and high performance liquid chromatography) and lipid biochemistry (including general mass spectrometry services). Core D (Animal Facilities) provides animal (mostly mouse) models by assessing genetically altered mutants or stock strains in maintaining them disease-free. Core E (Neuroimaging) provides for acquisition and quantitative analysis of data derived from functional, morphometric, and spectroscopy MR imaging and positron emission tomography. Core F (Behavior Science) offers training of subjects for cooperation with research protocols, selection and administration of standardized tests (developmental, cognitive and functional), direct observations of behavior, and design of activation paradigms for fMRI. The core units serve 62 projects representing current direct annual NIH support totalling over 14 million dollars. The program addresses 14 of the 21 priority areas set forth in RFA HD-87-003, featuring interdisciplinary collaboration and a theme, brain mechanisms whereby genotypes result in specific cognitive and behavioral phenotypes of mental retardation or developmental disability.